Adrenaline mediates a positive feedback loop in noradrenergic transmission: its possible role in development of...

Adrenaline activates prejunctional beta-adrenoceptors of the beta 2-subtype on sympathetic nerve terminals and enhances noradrenergic transmission. Adrenaline can be incorporated in transmitter stores of noradrenergic nerves and, when released as a cotransmitter, activates the prejunctional beta 2-adrenoceptors, thereby mediating autofacilitation of noradrenergic transmission. Adrenaline released from the adrenal medulla in stress may be incorporated in noradrenergic transmitter stores and reach a sufficient concentration as a cotransmitter to activate the autofacilitatory feedback loop involving prejunctional beta 2-adrenoceptors, resulting in prolongation of the increases in vasomotor tone and cardiac activity that occur acutely: with frequent repetition of stress, there may be progression into a hypertensive state. In accord with this hypothesis, adrenaline administration produces persistent increases in blood pressure in rats, and plasma levels of adrenaline are elevated in a proportion of hypertensive patients; furthermore, repeated stress produces prolonged increases in blood pressure in animals and man.